Method and apparatus for cryogenic spray ablation of gastrointestinal mucosa

ABSTRACT

A method and apparatus to treat Barrett&#39;s tissue, a pre-cancerous condition, by removing the epithelium above the lower esophageal sphincter through cryo-ablation. An endoscope with fiber optics is used to view the operation, and a catheter for supplying liquid nitrogen is passed through the lumen of the endoscope. Liquid nitrogen at low pressure is sprayed directly onto the Barrett&#39;s tissue through the catheter while the physician views the operation through the fiberoptics of the endoscope and controls the spray via a valve. Freezing is indicated by whiteness and shows that the epithelium has been cryoablated. The apparatus can also be used to treat various other gastrointestinal tract lesions. The catheter is insulated to withstand extremely cold temperatures without becoming stiff and without affecting the inherent flexibility and maneuverability of the endoscope.

RELATED APPLICATIONS

This application is related to Provisional Application Serial No.60/047,484 filed May 23, 1997 and is a continuation-in-part of Ser. No.09/050,150 filed Mar. 30, 1998, now U.S. Pat. No. 6,027,499.

FIELD OF THE INVENTION

The present invention relates to method and apparatus for the thermalablation of the interior lining of an organ, and more particularly fordestruction of Barrett's tissue and other lesions of thegastrointestinal tract by cryo-ablation of the gastrointestinal mucosa(gastrointestinal tract lining).

REVIEW OF THE RELATED TECHNOLOGY

Barrett's esophagus is a recognized precursor to 50% of all esophagealcancers. The incidence of esophageal cancer is rising and this diseaseis now among the top 15 cancers (Blot et al, JAMA, 270:1320 [1993]).Barrett's tissue has been found in 10% of an asymptomatic populationundergoing upper gastrointestinal endoscopy.

Standard therapy for esophageal cancer is removal of the esophagus, withmortality rates up to 37%. Treatment of this cancer costs $25,000 to$50,000 dollars per patient.

Barrett's esophagus is characterized by abnormal cell growth along theinner lining of the esophagus above the lower esophageal sphincter.Recent studies have demonstrated that when the metaplastic columnarepithelium characteristic of Barrett's is removed, healing replaces theBarrett's tissue with normal stratified squamous epithelium (Samplineret al, Gastrointestinal Endoscopy, 44:532-535 [1966]). This presumablyreduces the risk of cancer.

Lives would be saved if Barrett's tissue could be removed quickly,inexpensively, and with low risk. However, the only available procedureshave been slow, costly, uncomfortable, and/or dangerous. As a result,Barrett's esophagus goes untreated in many patients, whose healthsuffers.

The known ablation treatments for Barrett's esophagus include lasertreatment (Ertan et al, Am. J. Gastro., 90:2201-2203 [1995]), ultrasonicablation (Bremner et al, Gastro. Endo., 43:6 [1996]), photodynamictherapy (PDT) using photo-sensitizer drugs (Overholt et al, Semin. Surq.Oncol., 1:372-376 (1995)), and multipolar electrocoagulation such as byuse of a bicap probe (Sampliner et al, supra). The treatments are oftenmade with the aid of an endoscope.

Both sonic and light treatments require expensive apparatus and treatonly a small area at one time, so that an operation to remove theBarrett's tissue becomes tedious as well as more costly. One reportedtreatment with Nd:YAG laser used a 2.2-mm beam to treat large areas ofthe esophagus (Ertan et al, Am. J. Gastro. 90:2201-2203 [1995]).Furthermore, such therapies are often accompanied by esophagealstrictures and significant patient inconveniences; since total avoidanceof sun exposure and bright light is required for one month afterphotodynamic therapy.

Another problem is that there is no visual indication of which tissueshave been treated, or the extent to which tissues have been treated. Thephysician, looking through an endoscope, cannot see the effects of thesound or light directly.

Cryotherapy of the esophagus via direct contact with a liquid nitrogencryoprobe (metal probe cooled to a low temperature) has been studied inboth animal models and humans (Rodgers et al, Cryobiology. 22:86-92(1985); Rodgers et al, Ann. Thorac. Surq., 55:52-7 [1983]) and has beenused to treat early esophageal cancer (Grana et al, Int. Surg., 66:295[1981]). Disadvantages of this modality include the necessity for directmucosal contact, which temporarily binds the probe to the esophagus,potentiating the risk of esophageal perforation and inability to controlthe exact area of mucosal ablation. Rodgers et al states that acryoprobe must include a heating element to allow it to be removed. Thisprecludes removal of the probe until thawing has occurred. The depth ofthe injury with a solid cryoprobe cannot be reliably controlled. If thetip heater malfunctions, or timing is not precise, the depth of freezingcan become dangerous. In spite of the heating element, cats died fromesophageal lesions in some cases, apparently caused by freezing toodeeply and destroying the esophageal wall entirely. These studieshighlight the fact that controlling the amount of tissue that isirreversibly damaged by cooling is one of the main problems withcryosurgery.

Use of a bicap electrocoagulation probe has been suggested as a meansfor ablation of Barrett's esophagus (Heier et al, Gastro. Endo., 43:185[1996]). The use of a bicap electrocoagulation probe also suffers frommany disadvantages. Since the tip is small and must be repeatedlyenergized, the operation will be slow and time-consuming. Furthermore,the depth of injury is difficult to control. Esophageal perforationcould occur with excessive duration of the electrocautery current.

All the known ablation treatments using sound, light, or heat alsosuffer from another defect, a defect common to all: penetration of thedamage. The treatments cannot be adjusted to destroy only the very thinlining with the Barrett's tissue; underlying tissue is destroyed aswell.

As flesh is somewhat transparent to both sound and light, these energieswill penetrate some distance below the surface. The proportion of energyabsorbed by the tissue is generally constant, and so, at least to afirst approximation, the intensity of the light or sound will fall offexponentially with depth. Therefore, the amount of tissue damage willalso tend to decrease exponentially with distance. There is consequentlyno sharp line of demarcation between destroyed tissue and tissue whichis not affected: the degree of damage decreases continuously. Healthytissue is damaged along with diseased tissue.

The same type of damage results from heat probe or cryoprobe treatments.When the surface temperature of flesh is raised, heat travels byconduction into the tissue. The penetration of the heat—thetemperature/depth function—depends on the surface temperature, theexposure time, and the heat capacity of the hot probe in contact withthe surface. The degree of damage at any one depth depends on thetemperature reached. Similar problems are involved with the freezingassociated with contact by a solid cryoprobe.

Clearly, to raise the tissue temperature to a damaging level in only athin layer of epithelium, heat must be applied quickly from a veryhigh-temperature probe. However, this creates problems of possiblesticking and require precise timing of the hot probe contact duration,lest heat penetrate too deeply.

Complicating the use of heat, there is also a time factor. Not only thepeak temperature reached by tissue, but also how long the tissue “bakes”at the high temperature, determines the amount of damage. (This is thereason cold water should be put onto a burn, even after the bum is awayfrom heat.)

With none of the existing therapies is one able to precisely control thedepth of tissue damage while maintaining a sharp demarcation betweendamaged and undamaged tissue, with the physician being able to observethe precise location and degree of damage as it occurs. Ideally, theBarrett's tissue should be destroyed with the direct visualization andcontrol by physician in a manner which avoids any substantial damage toadjacent healthy tissue.

SUMMARY OF THE INVENTION

The present invention overcomes the drawbacks of the prior art by usinga direct spray of cryogenic liquid to ablate Barrett's tissue in theesophagus. Liquid nitrogen, an inexpensive and readily availableliquified gas, is directed onto the Barrett's tissue through a tubewhile the physician views the esophagus through an endoscope. Theapparatus and method of the present invention can be used to causecontrolled damage to the mucosal layer at any location in thegastrointestinal tract in a manner in which re-epithelialization canoccur. They can be used not only for the treatment of Barrett'sesophagus, which is the preferred application of the present invention,but also for the treatment of any mucosal gastrointestinal lesion, suchas tumor, polyps and vascular lesions. The apparatus and method can alsobe used for the treatment of the mucosal layer of any luminal area ofthe body which can be reached by an endoscope.

Liquid nitrogen spray has several distinct advantages over the priorart:

1) As compared to some of the prior art therapies, there is a sharpdemarcation between damaged tissue and non-damaged tissue. Above thefreeze surface, all the cells are killed; below, they are not harmed.Thus, it is possible to ablate the Barrett's, or other gastrointestinaltract lesions, without damaging the underlying tissues. This minimizesboth the trauma and the risk of infection.

2) Unlike a solid cold probe, liquid nitrogen cannot stick to tissue andcause severe frostbite.

3) The layer of destroyed tissue is thinner than with previoustherapies, including solid-probe cryotherapy, and this again minimizesthe damage as compared to the prior art. The reason that the liquidnitrogen spray can freeze a thinner layer than prior-art therapies isthat it instantly boils when it touches flesh, because the temperaturedifference is usually more than 200° C. Liquids have high thermalconductivities, and to boil a liquid requires large amounts of heat (thelatent heat of vaporization). These two factors together mean that heatis removed from the surface of the tissue at an extremely high rate, andbecause of this rapid surface cooling the freezing depth can be veryshallow. The temperature differential in the flesh is much higher thanit is with a hot metal probe because heat does not need to travelthrough a metal; the temperature is generated at the surface itself As aresult, the tissue surface can be frozen to well below zero before thetissue just under that frozen tissue has a chance to appreciably drop intemperature.

4) Freezing kills cells, but connective tissue and other body substancesare not damaged. Thus, the trauma is less as compared to heat burns.Shepherd et al, Cryobiology, 21:157-169 [19841]).

5) The cryoablation procedure requires only 15-20 minutes. Animalstudies have been done both under general anesthesia and under conscioussedation. Thus, the procedure can be performed on adult humans with alocal anesthetic or possibly without any anesthetic at all. Freezing isless painful than other methods of killing tissue because coldinherently anesthetizes the nerves. As the operation of the presentinvention can be performed without general anesthesia, the cost anddanger are both reduced still further over treatments employed by theprior art.

6) The cost of the procedure is minimal compared to that of the priorart, not only because of the short time for the operation and therelative safety (reducing insurance costs) but also because the capitalcost is relatively low. No special medical grade of liquid nitrogen isrequired. A storage canister can presently be refilled with liquidnitrogen by a commercial gas service for a delivery fee of approximately$20, plus about $3 per liter for the liquified nitrogen itself. Onetreatment will use approximately a liter or less. The cost for nitrogencan be as low as $30 per month even if only one treatment is performedduring that period.

7) The procedure can be conducted in such a manner as to allow constantvisualization by the physician of the tissue damage as it occurs. Meansare provided for removal of moist air at the distal end of the endoscopewhile dry nitrogen is sprayed. Thus, fogging of the endoscope lens canbe substantially avoided, allowing clear observation of the procedure asit occurs.

In order to realize the benefits of liquid nitrogen spray in theesophagus, the present invention provides these features:

(1) A standard “diagnostic” endoscope can be used, which is almostuniversally available to medical personnel, although a standard“therapeutic” endoscope can also be used. These relatively expensivepieces of equipment need not be purchased for the procedure.

(2) The endoscope allows the physician to see inside the esophagus anddirect the spray of nitrogen. Unlike prior-art therapies, the presentinvention allows the physician to see what areas have been frozen to alow temperature because the esophageal wall frosts and turns white. Thefrosting lasts for several seconds because the entire inside of theesophagus is at a low temperature, hovering near freezing during theoperation. This is due to the large amounts of cold nitrogen gasgenerated by boiling of the liquid nitrogen. Thus, it is possible forthe physician not only to know what areas are frozen, but what areashave been frozen recently. This allows a systematic progress ofcryotherapy over the area of Barrett's tissue without over-freezing ornon-freezing of any area.

(3) The endoscope can be disposed with fiberoptics, a T.V. camera and adisplay screen to allow the surgeon to view the treatment and treatedarea of the esophagus.

(4) The liquid nitrogen delivery equipment can be very inexpensive bymedical standards. Nitrogen may be delivered through a catheter ofstandard flexible tubing, such as TEFLON tubing. Plastic tubing isuniversally available, inexpensive, and safe because of its low thermalconductivity, which prevents the tubing from sticking to the esophagealwall. Other materials superior to TEFLON could be used.

(5) The flow of nitrogen can be controlled by a simple, reliable, andlow-cost delivery system. The nitrogen container is pressurized to pushthe liquid through the catheter. In one embodiment of this invention,the flow is hand-controlled by the pressure via a valve located at thenitrogen storage container. If more precise control is needed, theliquid nitrogen may be pumped directly or the flow may be controlled bya valve close to the proximal end of the catheter. As an example, asolenoid valve can be used.

(6) If a more rapid delivery of liquified gas is required, a pressurebuilding tube or coil for supplying heat can be provided on the nitrogencontainer or tank. Actuating this pressure building coil causes theliquid nitrogen to build up pressure in the container thus allowing thenitrogen to be more rapidly delivered to the catheter.

(7) During cryosurgery, the invention provides for removal of gasgenerated by the brisk boiling of liquid nitrogen. Removal is necessaryfor several reasons: first, the gas will build up a dangerous pressureif there is no escape path; second, the gas will tend to enter thestomach and bloat it because the esophagus is at least partially blockedby the endoscope, and the lower gastrointestinal tract presents a pathof lessened resistance; third, the gas boiled off from the esophagealsurface may be at a sub-zero temperature and should be removed toprevent over-freezing; and fourth, the initially moist air can beremoved so as to avoid substantial condensation on the endoscope lens.

(8) The inventors have found that in using the cryospray in therelatively enclosed esophageal cavity the pressure of the spray is to bereduced. If the pressure is not reduced, the high volume of gas couldunduly expand in the esophageal cavity and cause patient discomfortand/or rupture of vital tissue. In order to produce a cryogenic spray ofreduced pressure, this invention proposes a vent between the gas supplytank and the catheter. Other methods for reducing pressure areenvisioned by this invention.

(9) Importantly, the catheter is supplied attached to a vent. Acatheter, not supplied with such a vent, will deliver a high pressurespray which could be injurious to internal tissue. As pointed out,methods other than a vent could be used to reduce pressure.

(10) The catheter employed by this invention is made of a material whichis not brittle, such as PTFE and polyamide. In addition, the catheter isto be insulated. The catheter is designed to withstand extremely coldtemperatures without becoming stiff and brittle and without affectinginherent flexibility and maneuverability of the endoscope. For example,the insulated catheter should be capable of withstanding temperaturesdown to −100° C. The temperature of gas sprayed at the tip isapproximately between −20° C. to −50° C. However, higher and lowertemperatures are contemplated by the inventors.

(11) The invention herein disclosed contemplates treating precancerouslesions.

The herein disclosed invention contemplates treating various internallesions with a low pressure cryogenic spray. Low pressure can bedetermined by routine experiment by those skilled in the art. Theinventors have found a pressure of approximately 3-5 psi to beoperative. In addition, pressures up to around 45 psi would beeffective.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

FIG. 1 is a partially schematic overview showing use of the apparatus ofthe present invention.

FIGS. 1A, 1B and 1C are enlarged views of the placement of the endoscopeand catheter in the esophagus.

FIG. 2 is a perspective end view of an endoscope with a protrudingcatheter. Part of the endoscope and catheter have been broken off forease of illustration.

FIGS. 3-5 are perspective views of alternate embodiments of the cathetertip.

FIG. 6 is a partial schematic view of the improved cryosurgical system.

FIG. 7A is a perspective view of a tank and valve arrangement used todeliver liquified gas to the catheter. Part of the tank has been brokenaway for ease of illustration.

FIG. 7B is a perspective view thereof with the tank turned 90°.

FIG. 8 is a top plan view thereof

FIG. 9 is a perspective view of an electronic control box and printer.

FIGS. 10A-F are views illustrating a combined catheter, bleeder vent andluer lock fitting attached to a solenoid valve fitting. The catheter hasbeen broken away for ease of illustration.

FIG. 11 is a packet or kit containing a combined catheter, bleeder ventand luer lock fitting along with a nasogastric tube.

FIG. 12A is a schematic block diagram of the cryosurgical apparatus andprocess of the present invention.

FIG. 12B is a “closed loop” schematic block diagram of the cryosurgicalapparatus and process of the present invention.

FIG. 13 is a flow chart describing the cryosurgical procedure.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIG. 1, an apparatus and method for cryo-surgical ablationof Barrett's esophagus has an endoscope 10 inserted into the esophagusE, of a patient P, adjacent to the stomach S. Barrett's tissue B linesthe esophagus E above the lower esophageal sphincter.

A conventional therapeutic endoscope 10 is illustrated in the drawings,although a smaller diagnostic endoscope is preferably used from thestandpoint of patient comfort, particularly when a balloon shield is notbeing used. A specially designed endoscope can also be used. The distalend 12 of such an endoscope 10 is shown in FIG. 2, showing an imagingcamera lens 14, illuminating light 16, biopsy channel (bore or lumen) 18with the catheter 20 therein, and an additional lumen 22. The imagepicked up at the lens 14 is transferred via fiber optics to a monitoringcamera 25 (FIG. 1) which sends TV signals via a cable 26 to aconventional monitor 28, where the procedure can be visualized. Byvirtue of this visualization, the surgeon is able to perform thecryosurgery in the esophagus.

Through the lumen 18 is disposed a catheter 20, preferably aconventional TEFLON catheter size 7 FR of 2-3 mm outside diameter. Thecatheter 20 protrudes from the distal end 12 (i.e., the end firstinserted into the esophagus) of the endoscope 10 and extends to theproximal end 30 (closest to the operator, outside the patient) where aphysician's hand H1 guides the catheter 20. As seen in the monitor image28 of FIG. 1, the distal end 12 of the catheter 20 may be bent at anangle.

The catheter 20 is coupled to a tube extending near the bottom of aDewar flask 32 filled with liquid nitrogen or other liquified gas LG. Asused in the present specification, “gas” in the phrase “liquified gas”means any fluid which is physiologically acceptable and which has asufficiently low boiling point to allow the cryotherapy of the presentinvention. For example, such boiling point is preferably below about−150° C. The gas is preferably nitrogen, as it is readily available, oralternatively argon.

The Dewar flask 32 may be adapted from an ordinary commercial containersuch as a THERMOS bottle holding as little as a quart of liquid, whichcan readily be refilled from a larger container. Liquid nitrogen is alsoeasily and safely handled in foam-insulated containers (e.g., STYROFOAMcups). However, the container 32 is preferably a medium-capacitystainless-steel Dewar flask of several liters capacity. A largercontainer, able to provide liquid for numerous operations over severalweeks time, may be used. For expediency the large container may bemounted on a cart.

The Dewar flask 32 is closed and the interior space is pressurized witha small air pump 34, which may alternatively be mounted in the containerlid or elsewhere.

FIG. 1 shows schematically that the proximal end of the catheter 20 iscoupled to a tube 35, preferably by a standard luer lock 37, and thelower end of the tube 35 is immersed in liquid nitrogen LG while theinterior is pressurized by a free-running pressure pump 34 through atube 38. A pressure gauge 40 is preferably provided, or alternatively asafety valve with a preset opening pressure (not shown). The pressure isselected so as to permit adequate spray from the distal end of thecatheter 20. The interior of the Dewar flask 32 is vented through a venttube 42 which is preferably opened and closed by a valve operated by thephysician's hand H2. FIG. 1 shows the thumb obstructing the end of thevent tube 42. When the vent is closed, pressure builds up in the Dewarflask 32 and nitrogen is pumped through the tube 35 to catheter 20.

While the valve is shown as a simple thumb-valve in FIG. 1, it will beunderstood that such a valve could be a mechanical valve or anelectromechanical valve, preferably controlled by a trigger mechanism,or the like, as could be readily envisioned and constructed by those ofordinary skill in the art. In a preferred embodiment of this invention,an electrically operated solenoid valve is employed in delivering theliquified gas to the catheter. Of course, the solenoid is specificallyadapted to function properly at cryogenic temperatures.

The vent tube 42 is left open until the physician has positioned thecatheter near the Barrett's tissue, as guided by the hand H1 andconfirmed by viewing the monitor 28. The physician then closes the vent42 and liquid nitrogen is pushed into the proximal end of the catheter20 at the luer lock 37.

As the liquid nitrogen moves through the catheter 20, it starts to boiland cool gas rushes ahead to emerge from the distal end or catheter tip46. The amount of boiling in the catheter 20 depends on the mass andthermal capacity of the catheter. Since the catheter is of smalldiameter and mass, the amount of boiling is not great. (The catheterwould preferably be “French Seven”.) After the catheter is cooled to alow temperature, and becomes filled with liquid nitrogen, the liquidnitrogen reaches the distal end of the catheter 20 near the distal endof endoscope 12 and begins to spray out of the catheter onto theBarrett's tissue. It is to be noted that the present invention may beable to freeze the Barrett's tissue sufficiently without actual liquidnitrogen being sprayed from the catheter, and that a spray of liquid maynot be needed if the very cold gas can accomplish the task of freezingthe epithelium.

Freezing is apparent to the physician by the frozen tissue B acquiring awhite color (cryoburn), due to surface frost (visible on the monitor 28in FIG. 1); the white color indicates gastrointestinal mucosal freezingsufficient to destroy the diseased tissue. The physician manipulates theendoscope 10, vent 42, and/or catheter 20 to freeze all of the Barrett'stissue. Once the operation is complete, the endoscope 10 with catheterare withdrawn.

The invention also contemplates valving the nitrogen at the distal endof the catheter, immediately adjacent the Barrett's tissue. Apparatusfor such valving 53, shown in FIG. 3 and discussed below, allows forcontrol of the liquid nitrogen flow.

Since there is no gross damage to the esophagus (for example, there isno laceration), there is no need to treat the frozen area. The columnarcells of the Barrett's tissue soon die, and the lining is sloughed offto be replaced by healthy squamous tissue.

Because the invention uses liquid spray via a catheter 20 rather thancontact with a cold solid probe, there no risk of a cold apparatussticking to the esophagus and tearing the tissue. The plastic materialof the catheter, such as TEFLON, is in little danger of sticking to thetissue because of its low thermal conductivity and specific heat.Furthermore, it is not designed to touch the tissue.

Using a catheter the cooling rate (rate of heat removal) is much higherthan with a solid probe since the sprayed liquid evaporates directly onthe tissue to be frozen, which absorbs the entire heat of vaporization.The rate of rewarming is also high, since the applied liquid boils awayalmost instantly. No cold liquid or solid remains in contact with thetissue, and the depth of freezing is minimal.

Since freezing is accomplished by boiling liquid nitrogen, large volumesof this gas are generated. This gas must be allowed to escape. The localpressure will be higher than atmospheric since the gas cannot easilyflow out of the gastrointestinal tract; nitrogen gas will tend to enterthe stomach S, whose junction with the esophagus (the esophagealsphincter) is immediately adjacent to the Barrett's tissue freezingzone. The present invention provides for the gas to escape by severalalternate methods.

First, the stomach may be suctioned with a separate tube 41. Forexample, a nasogastric tube 41 as seen in FIGS. 1A, 1B and 1C, whichpreferably runs outside of and adjacent to the endoscope 10. Suction maybe provided by a suction pump 45 or other conventional means forsuction.

Second, an escape path may be provided by an additional lumen in theendoscope. Additional lumens are provided on so-called “therapeutic”endoscopes. “Diagnostic” endoscopes typically have only one lumen, whichwould be occupied by the liquid nitrogen-delivery catheter 10 when suchan endoscope is used in the present invention. The use of a two-lumen“therapeutic” scope in the present invention provides an extra lumen foruse as an escape path for gas venting. The application of suction tosuch a vent lumen is also preferably provided.

The lower esophageal sphincter may be blocked with an inflatable balloon43 (FIGS. 1A and 1B), or some other shield, to prevent nitrogen gas frominflating the stomach. The balloon 43 may be of the “TTS” (through thescope) type, passing through an additional lumen on the endoscope as isshown in FIG. 1. Alternatively, a balloon may be placed alongside theendoscope 10, such as an achalasia balloon. A bulb 44 or some othermeans for inflating and deflating the balloon 43, such as a hand pump,can be provided. This may optionally be used in conjunction with stomachsuction.

FIG. 2 shows a catheter tip 46 fastened on the end of the catheter 20and adapted to spray liquid nitrogen in a radial pattern through pluralholes 47 between the surface and an interior space fed by the catheter20. The length of the tip 46 is preferably chosen so that the entirearea of the Barrett's tissue is frozen at once without the need formanipulating the endoscope or catheter to freeze the Barrett's area insequential increments. The tip 46 may be of rigid material such as metalor stiff plastic, preferably the latter. Alternatively, the entireendoscope and/or catheter may be moved up or down the esophagus toensure that the entire Barrett's area is sprayed.

FIG. 2 also shows the distal end 12 of the endoscope 10 including acamera lens 14, illuminating light 16, biopsy channel or lumen 18 withthe catheter 20 therein, and an additional lumen 22. The endoscope shownin FIG. 2 is a conventional therapeutic endoscope. A diagnosticendoscope would lack extra lumen 22.

Alternatively to FIG. 2, the catheter 20 itself may include a pluralityof radial holes 49 and an end plug 50 (FIG. 5) to force the nitrogen toflow out of the radial holes. The end plug 50 is controlled by a wire(not shown). The catheter tubing, even though of plastic, becomes muchmore rigid at very low temperatures and approximates the stiffness ofthe separate tip 46.

FIG. 3 depicts a wire-controlled end valve embodiment in which a tip 52interacts with a disc 53 proximally controlled by the physician via awire 54 running through the inside of the catheter 10. The liquidnitrogen hits disc 53 and becomes atomized into a radial spray.

FIG. 4 shows an end 56 of the catheter 20 cut at an angle to deflect thespray to one side.

With reference to FIGS. 6-9, a particularly elegant and preferred gassupply system 70 is described. In this system, a pressurized gas tank 72is employed. A convenient size for the tank has been found to be a 5.5liter tank, and of course larger (e.g. 35 liter) or smaller size tank oreven a canister would be operative. The inventors have found a doublewalled insulated tank (not shown) to be convenient because with adequateinsulation the very low temperature of the liquid nitrogen gas can bemaintained over a long period of time. The inventors have found theoptimum pressure for the liquified gas in the tank to be 22 psi. Theinventors have found 22 psi to be operative but higher or lowerpressures are also operative.

Tank 72 is equipped with a pressure building coil or tube 74 formaintaining pressure. This coil 74 consists of metal tubing running frominside the tank to outside the tank and returning back to inside thetank. The tube 74 in operation contains circulating liquid nitrogen. Ifthe pressure in the tank 72 drops below acceptable levels, valve 75 tothe tube 74 can be opened to circulate gas outside of tank 72 throughthe tube 74. The nitrogen liquid in the tube outside the tank will bewarmed and returned to the tank. This warmed nitrogen liquid will boostthe head pressure in the tank 72 and allow for more rapid delivery ofnitrogen liquid to the catheter. In the tube arrangement shown, thevalve 75 is hand operated, however, the valve could be automatic andwould start circulating liquid through the tube or a coil once thepressure drops to unacceptable levels in the tank and to stopcirculating once the pressure returns to normal. With normal pressuremaintained in the tank, liquified gas will be more rapidly expelled fromthe tank to the catheter. The force of gas expelled from the tank is afunction of the temperature and pressure of the liquid nitrogen in thetank. Because of the large temperature differential between the ambienttemperature and the temperature of liquid nitrogen, only a short lengthof tubing 74 is required.

The gas supply system 70 illustrated in FIGS. 6-8 has a tank 72 equippedwith valves and gauges. The tank 72 is equipped with a head gas valve 77for relieving head pressure and a liquid nitrogen valve 78 which isopened to allow liquid nitrogen to flow to the solenoid valve 80 andthen to catheter 20. There are safety relief valves 81, 82 on the tank72 which relieve at pressures greater than 22 and 35 psi, respectively.In addition, the tank is equipped with a head pressure gauge 83 and aliquid level gauge 84.

The improved cryosurgical gas delivery system 70 has improvements whichallow the physician to more accurately and comfortably deliver thecryogenic gas to the patient. The improved system 70 has a foot-pedaloperated solenoid valve switch 86 (FIGS. 6 and 9). This foot-pedaloperated solenoid valve switch 86 actuates solenoid 80 between the tank72 and catheter 20. The foot pedal 86 has the advantage of allowing thephysician's hand to be free during cryosurgery. Note, for example, thatthe system with the Dewar flask (FIG. 1) requires the physician's thumbto close vent 42 to produce pressure in the Dewar flask causing nitrogengas to flow. The improved tank 72 heating coil or tube 74 and foot-pedaloperated solenoid switch 86 allows for quick delivery of adequateamounts for cryogenic spray to treat Barrett's esophagus or other tissuerequiring cryoablation.

Referring to FIGS. 6-8 and 10, an elegant design feature of the improvedsystem 70 is the ability of the system to force super-cooled nitrogengas through the catheter 20 at low pressure. This feat is possiblebecause the improved system has an auxiliary bleeder vent or bleeder 88positioned between the liquid nitrogen gas supply tank 72 and thecatheter 20. The bleeder is positioned at a point in-line where theinternal diameter of the system (i.e., catheter) is significantlyreduced. This bleeder vent is designed to eliminate the elevatedpressure produced at the catheter caused by the reduced internaldiameter of the catheter relative to the larger internal diameter of thetube supplying gas to the catheter; and by the volatilization of theliquid nitrogen to gas phase nitrogen. This bleeder 88 reduces pressurein the catheter 20 and at catheter tip 46 by venting gas phase nitrogenout the bleeder vent 88. With this venting of gas phase nitrogen, liquidphase nitrogen exits the catheter tip 46 as a mist or spray at apressure of approximately 3-5 psi compared with the tank pressure ofapproximately 22 psi. Improved embodiments of this invention do notrequire a bleeder vent.

As an exemplary embodiment the vent may simply be a piece of tubingattached to the liquid nitrogen supply by a “T” connection. As theliquid nitrogen makes its way from the tank 72 to the proximal end ofcatheter 20, the liquid is warmed and goes to gas phase. This phasechange creates additional pressure throughout the length of thecatheter, but is especially important at the solenoid/catheter junction,where the diameter of the supply tube relative to the catheter lumendecreases from approximately 0.5 inches to approximately 0.062 inches,respectively. Note that, in order to force low pressure liquid/gasnitrogen through this narrow opening, either the pressure of thesupplied nitrogen must decrease or the diameter of the catheter mustincrease. The inventors did not wish to employ a highly pressurizedsystem, nor did they wish to enlarge the catheter diameter. Accordingly,the auxiliary bleeder 88 allows the liquid phase nitrogen to passthrough this reduced diameter catheter without requiring modification oftank pressure or catheter diameter. Without a pressure bleeder vent, thepressure of gas leaving the catheter would be too high and have thepotential for injuring the tissue of the gastrointestinal tract.

The pressurized tank can be provided with a bleeder or bleed-off toassure that the pressure of the cryogenic spray discharged from the tipof the catheter does not inadvertently injure the patient.

While a Dewar flask (FIG. 1) is illustrated and was used in theexperiments reported below, it should be understood that the liquifiedgas source can be of any type. For example, a pressurized tank or areservoir, such that the liquified gas is piped into a connecting siteon the procedure room wall. The main requirement being that theliquified gas supply be controllable by the physician.

It is an important preferred feature of the present invention that thespray be conducted in such a manner as to allow constant visualizationby the physician of the tissue treatment as it occurs. If thetemperature of the lens at the proximal end of the endoscope dropsprecipitously at the start of the liquid nitrogen spray, the moist airof the esophageal environment or of the air of the catheter which hasbeen blown out ahead of the nitrogen flow will condense on the lens,thereby obscuring the physician's view of the operative site. This canbe substantially avoided by means of the suction pump 45 which willimmediately suck out the moist air which is present prior to the arrivalof the liquid nitrogen spray or cold nitrogen gas. Because of thispumping out of the moist air as the spray commences and the replacementwith extremely dry nitrogen gas, substantial amounts of moisture willnot form on the lens 14 during the procedure, allowing an excellent viewof the operative site by the physician during the procedure.

This condensation effect is augmented by the fact that the catheteritself is preferably not wrapped in additional insulation. This causesthe temperature of the nitrogen gas exiting the catheter at the distalend to be relatively high at the beginning of the spraying operation andgradually cooling as the catheter cools. Indeed, in the tests conductedin the esophagus of pigs discussed below in the Examples, often 10-20seconds were necessary before significant freezing was seen through theendoscope. If the catheter is substantially insulated, the interior ofthe catheter will cool much more quickly as it will not be picking upheat from the outside. With this insulated catheter, it is to beexpected that the liquid nitrogen would be sprayed onto the tissuealmost immediately, causing much faster freezing and, thus, allowingless control on the part of the physician.

Another reason that the lens does not fog or frost in the presentinvention is that the esophagus is flushed out with nitrogen gas, whichis extremely dry. The nitrogen gas is moisture free because the liquidnitrogen is condensed out of atmospheric gases at a temperature −197° C.colder than the temperature at which moisture is condensed out.

The combination of relatively warm, and completely dry nitrogen gas,together with suction flushes all moist air from the esophagus. As thetemperature of the gas entering the esophagus falls, so does the surfacetemperature of the camera lens 14. Ordinarily at that time the lens 14would be cold enough to condense moisture and fog, however, since theesophagus is dried out (in contrast to its usual highly moist state)there is no moisture to condense. Thus, the lens 14 stays un-fogged andun-frosted and continues to provide a clear view of the operation. Onthe other hand, if the esophagus is not vented with suction and/or theesophagus is not preliminarily flushed with dry nitrogen gas (perhapsbecause the catheter is insulated, lowering its heat capacity, and/orthe nitrogen delivery pressure is too high), then the lens is likely tofog or frost and the physician cannot operate effectively.

In order to deal with the moist air problem, there is supplied in thepreferred embodiment of this invention a nasogastric tube 41 (FIGS. 1and 1A-1C). During the cryosurgical procedure the nasogastric tube isinserted prior to inserting the endoscope 10 and catheter 20. Thenasogastric tube 41, when connected to a pump 45, can serve to evacuatemoist air from the esophagus prior to cryosurgery. With moist airremoved, the T.V. camera lens 14 is not obscured by fog and thephysician can perform cryosurgery with an unobstructed view.Alternatively, if fogging occurs during cryosurgery, the nasogastrictube and pump can be used to evacuate the esophagus.

In the most preferred embodiment, the composition of the catheter or thedegree of insulating capacity thereof will be selected so as to allowthe freezing of the mucosal tissue to be slow enough to allow thephysician to observe the degree of freezing and to stop the spray assoon as the surface achieves the desired whiteness of color (cryoburn).The clear observation results from the removal of the moist air andsprayed nitrogen by the vacuum pump; in combination with the period offlushing with relatively warm nitrogen prior to application of the sprayof liquid nitrogen which is caused by the relative lack of insulation ofthe catheter. Preferably, the catheter has a degree of insulation whichpermits at least five seconds to pass from the time said means forcontrolling is opened to the time that liquified gas is sprayed onto themucosa.

With reference to FIGS. 6, 9 and 12, an electronic monitoring andrecording system 90 is illustrated. The electronic components of thesystem 90 comprise a temperature sensor or probe 92 and timer 96. Alsoconnected to the monitoring and recording system 90 are the foot-pedal86 for actuating the solenoid 80 and recording console 95. In FIG. 6 anelectric power cord 93 runs from solenoid 80 to control box 90.

The temperature sensor 92 is thin and can be inserted into the esophagusbeside the catheter 20. In a preferred embodiment, the temperaturesensor 92 and catheter 20 can be inserted separately or as an integralunit of sensor and catheter combined, or alternatively the sensor can beinserted through an extra lumen of the endoscope to come in contact withthe tissue of the esophagus. The temperature sensor 92 sends temperaturereadings to the electronic monitoring and recording system 90 forprocessing and recordation.

The liquid gas flow is started by actuating solenoid foot-pedal 86 andends with release of the solenoid foot pedal 86. The electronicmonitoring and recording system 90 records the times at which cryoburnstarts and ends. Temperature in the context of time will be recorded forthe cryosurgery. This recordation allows for better data acquisition anddocumentation.

There is an automatic cut-off if a time or temperature limitation isexceeded. In the event of a cut-off, the electronic monitoring andrecording system can be reactivated by pushing the reset button 98 (FIG.9). Current time and temperature readings are presented in the windows99 as LED numbers. The windows in FIG. 9 will indicate total time 100;shut-down time 101; cryotime 102; cryotime set 103; and temperature 104.Within the main console of the electronic monitoring and recordingsystem 90 of FIG. 9 is a printing unit 95 which prints and records 95the time and temperature during the cryoburn. Every event is recorded,e.g. time, on and off, temperature, etc. FIGS. 6 and 9 show alternativemodels of the electronic monitoring and recording system. The printedrecord 97 is shown in FIG. 9.

The electronic console can be preprogrammed to be patient specific.

The operating sequence of components used in carrying out applicant'sprocess are described in FIGS. 12A and 12B. FIG. 12A describes thenitrogen source 72, foot-actuated 86 solenoid valve 80, electroniccontrol box and printer 90, endoscope 10 with catheter 20 and T.V.monitor 28 for treating a patient with Barrett's Syndrome. In FIG. 12Bis shown a completely automated system with sensors and a microprocessorfor performing cryosurgery. The completely automated system of 12B issimilar to the system of 12A except that various sensors fortemperature, time, etc. 92 send an output signal(s) to a microprocessorcontroller 90 to control the shut-down of the system if pre-set limitsare exceeded or if pre-set conditions are not met.

The steps for performing the esophageal cryosurgical procedure aredescribed in flow chart FIG. 13.

The electronic circuitry for the electronic monitoring and recordingsystem 90 is described in FIGS. 14A and 14B.

The components or paraphernalia required to practice the method of thepresent invention may be packaged and sold or otherwise provided tohealth-care providers in the form of a kit. The kit is preferably sealedin a sterile manner for opening at the site of the procedure. The kitwill include the catheter, having the spray means at one end, as well asa means for connecting the catheter to the source of liquified gas. Thismeans for connecting may be a simple luer connection on the opposite endof the catheter from the spray means. However, the term “means forconnecting said catheter to a source of liquified gas” is intended toinclude any other device or apparatus which allows the catheter to beconnected to the gas source.

Many of the components of the cryosurgical system are conventionalmedical appliances. For example, the endoscope is a conventional medicalappliance and would not necessarily have to be supplied as part of akit. One of the components to be supplied in a kit or sterilized packageis a combined catheter-bleeder vent.

With reference to FIGS. 10A-10F and 11, this invention envisions thecatheter 106 at its proximal end being integrally provided with apressure reducing bleeder vent 107 as a single unit. The unit can beattached to the gas supply tube through a luer lock 37 connection andcan be supplied to the user in a sterile package or kit 108 (FIG. 11).

With reference to FIGS. 10A-10F, there is schematically represented tubeconnector 109 for connecting a tube running from the liquid nitrogensupply tank 72, to solenoid 80. The solenoid has a connector fitting towhich can be attached a vented catheter. The vented catheter comprisesas an integral unit a connector fitting 37 attached to the solenoid 80along with a vent 107 between the connector 37 and the catheter 106.

The catheter and bleeder unit can be supplied with various modificationsin the placement of the bleeder vent relative to the catheter. Inaddition, envisioned are a variety of reductions between the solenoidvalve and the catheter. For example, FIGS. 10A-10C show that the actualposition of the Bleeder relative too the catheter is open to designoptions. FIGS. 10A-10F show a blunt reduction (i.e., reduction occursjust before the catheter). FIGS. 10D-10F depict a tapered reduction(i.e. the diameter is reduced gradually over the entire length). Anotheroption would include stepping reductions. In addition, the inventorscontemplate that the vent can have a piece of tubing attached to leadaway gas and the placing of a strainer (similar to a colander) inside ofthe tubing from the solenoid to the catheter. This strainer would serveas a mechanical means for separating the liquid phase from the gasphase.

Note particularly that the solenoid valve is specially designed toaccept cryogenic gases and is commercially available.

Referring to FIG. 11, the inventors envision supplying the catheter andvent unit 105 as a separate item. In this way, the unit can be suppliedin a sterile packet or kit 108 to be used with existing equipment foundin hospital operating rooms. The kit may contain a nasogastric tube 41.

The means for controlling the flow of liquified gas to the catheter isalso preferably present in the kit and may be connected to or may bepart of the means for connecting the catheter to the source of liquifiedgas. For example, the connector may contain a valve therein or the valvemay be a separate element connected between the connector and thecatheter or between the connector and the nitrogen source.

The endoscope may either be part of the kit or an available conventionalendoscope may be used in conjunction with the remaining components ofthe kit.

The kit will also optionally contain the means for withdrawing gas, suchas a tube and a means connectable to the tube for withdrawing gas fromthe tube. Such means connectable to the tube for withdrawing gas may bea vacuum pump or any other device or apparatus which will accomplish thefunction of withdrawing gas from the tube. The vacuum pump is optionallyomitted from the kit as a source of vacuum is often found in hospitalrooms in which such a procedure is to take place.

The means for blocking the lumen is also optionally present within thekit. Thus, for example, the kit may contain a balloon catheter or anyother device or apparatus which can accomplish the function of blockingthe lumen when in use.

The term “container” or “package” when used with respect to the kit isintended to include a container in which the components of the kit areintended to be transported together in commerce. It is not intended tocomprehend an entire procedure room in which the individual componentsmay happen to be present, an entire vehicle, a laboratory cabinet, etc.The claimed “means for causing fluid flowing therethrough to be sprayedin a radial direction” is intended to comprehend the illustratedembodiments of catheter tips shown in FIGS. 2-5, as well as anyfunctional equivalents thereof. Any device which can be connected to theend of a catheter which will direct fluid in the catheter to be sprayedsubstantially radially may be used. The terminology “a radial directionsubstantially perpendicular to the axis of the catheter” is intended toinclude a unidirectional spray over a small arc in the radial plane oran omnidirectional spray through 360° of the radial plane, or any arctherebetween. The term “substantially perpendicular” is not intended tolimit direction of the spray to a plane at an angle of 90° to the axisof the catheter but to include any type of spray which will allow themucosa of the lumen, such as the esophagus which is coaxial to thecatheter to be sprayed, near the locus of the tip of the catheter and toexclude a spray which is only substantially axial. The claimed “meansfor controlling the flow of liquified gas” is intended to encompass thesimple thumb-valve illustrated in FIG. 1, as well as any othermechanical, mechano-electrical, etc., device that will accomplish thefunction of controlling the flow of liquified gas from the source to thecatheter. This includes any type of valve, including, for example, atrigger valve, a rotary valve, a stopcock, etc. The valve may bemanually controlled, electrically driven, remotely controlled, etc.Other means for controlling the flow of liquified gas are not excluded.

The claimed “means for withdrawing gas” is intended to include theillustrated tube 41 and vacuum pump 45, as well as any functionalequivalent thereof. It does not matter whether the tube withdrawing thegas passes through the endoscope, around the endoscope, or even isplaced into the area from which gas is to be withdrawn by incision. Theonly important function is the withdrawal of the gas from the area inquestion. While a vacuum pump is preferred, any other type of pump ordevice which will cause the withdrawal of the gas is intended to beencompassed by this terminology. Other means for withdrawing gas are notexcluded.

The claimed “means for blocking the lumen” is intended to encompass notonly the balloon catheter 43 and the shield of FIG. 3, but also anyother device or technique which will accomplish the function of blockingthe lumen, e.g., the esophagus when the condition being treated isBarrett's esophagus. Any manner of substantially preventing the gasbeing sprayed through the catheter from passing beyond the point ofblockage is intended to be included by this terminology, including, forexample, physically squeezing the lumen from the outside or chemicallycausing the lower esophageal sphincter to close, etc.

The claimed “means for forcing said liquified gas” is intended toinclude not only the illustrated pressure pump 34 but any other deviceor apparatus which will force the liquified gas from its source to thecatheter. This includes use of a pre-pressurized container of liquifiedgas or apparatus which causes gas to liquify and then be directlydirected to the catheter, etc. No manner of driving the liquified gasfrom the source to the catheter is intended to be excluded.

Each of the steps set forth in the method claims herein are likewiseintended to comprehend not only the specific acts described in thespecification but any other acts which will accomplish the function setforth in the method step. Thus, for example, the step of adjusting thecatheter may be accomplished by hand, as illustrated in FIG. 1, or byany other technique up to and including use of a complicated remotecontrolled robotic adjusting apparatus. The same is true for all of theother method steps for performing specified functions.

The inventors have concluded from preliminary test results that a 30second “cryoburn” time was adequate to ensure the appropriate tissuedestruction, and thus appropriate cellular healing of damaged tissue(this conclusion was based on a 30 day follow up period). “Cryoburn” isa term defined by the instance that the normally “pinkish” esophagealtissue turns white (much like freezer burn). A range for the “cryoburn”time could be 5-10 seconds to 2 minutes or more depending on thesubstrate to be treated.

Due to the nature of the system, “cryoburn” does not immediately occur,but rather requires that the entire fitting and catheter system becomecool. Typically this required approximately 20-30 seconds from the timethat the solenoid foot pedal is depressed, and liquid nitrogen isallowed to flow from the tank.

During animal testing the approximate temperature that cryoburn wasfirst observed was at approximately −10 degrees C. The temperature rangefor cryoburn would be approximately −10 to −90 degrees C.

In carrying out the procedure, a nasogastric tube is first inserted intothe esophagus, after which an endoscope is inserted. The endoscope issupplied with light and fiber optic T.V. camera. Optionally, attached tothe endoscope will be a temperature probe to sense the temperature andreport the temperature to the recording console. Once the nasogastrictube, endoscope and temperature probe are in place, the catheterattached to the gas supply will be inserted into a lumen of theendoscope. Before liquid gas is supplied, the esophagus is ventilatedusing the nasogastric tube to remove moist air from the esophagus (ifrequired). With the moisture evacuated and the endoscope is properlypositioned, gas can be supplied to the catheter by actuating thesolenoid with foot pedal. Once the solenoid is actuated gaseous nitrogenand then a spray of liquid nitrogen will come from the tip of thecatheter. The cryoburn will generally last for 30 seconds to 2 minutes.

EXAMPLE

The cryospray device of FIG. 1 was used in experiments to assess theefficacy and safety of this device in mucosal ablation in Me distalesophagus of swine. The catheter 20 was a long 7 Fr ERCP-like catheterplaced through the biopsy channel of an Olympus GIF-100 endoscope. Theswine were sedated using telazol and xylazine given intravenously.General anesthesia was not necessary. Liquid nitrogen was sprayed on thedistal 2 cm of the esophagus in 16 swine under direct endoscopicobservation until a white “cryo-bum” appeared, usually within 10-20seconds. Duration and location of the spray were varied to assesshistologic response and dept of “cryo-bur”. The swine were thenre-endoscoped on days 2, 7, 14, 21 and 30 to obtain biopsies from theinjury site, assess mucosal ablation and re-epithelialization. All swinewere then euthanized and underwent necropsy.

Freezing of the esophageal mucosa was recognizable by a white“cryo-burn” with sharply demarcated margins. This was followed by slowthawing within minutes and then mucosal erythema. Sixteen swineunderwent hemi-circumferential to circumferential cryotherapy of theirdistal esophagus varying the duration of “cryo-burn” from 10-60 seconds.Blistering and sloughing of the superficial mucosa occurred within 2 to7 days of the cryospray. Mucosal damage occurred only at the cryo site.Biopsies 48 hours after cryospray consistently demonstrated coagulativenecrosis involving the mucosal layer and biopsies 30 days aftercryospray consistently demonstrated complete re-epithelialization of theinjured area. Complications included one esophageal stricture and oneesophageal perforation in experiments with prolonged cryo-burn.

These experiments on living swine, which are a valid model of the humanesophagus, establish that cryotherapy spray of liquid nitrogen via upperendoscopy is a simple technique capable of inducing controlledsuperficial mucosal damage with complete healing in the esophagus.

The foregoing description of the specific embodiments will so fullyreveal the general nature of the invention that others can, by applyingcurrent knowledge, readily modify and/or adapt for various applicationssuch specific embodiments without undue experimentation and withoutdeparting from the generic concept, and, therefore, such adaptations andmodifications should and are intended to be comprehended within themeaning and range of equivalents of the disclosed embodiments. It is tobe understood that the phraseology or terminology employed herein is forthe purpose of description and not of limitation. The means andmaterials for carrying out various disclosed functions may take avariety of alternative forms without departing from the invention. Thusthe expressions “means to . . . ” and “means for . . . ” as may be foundin the specification above and/or in the claims below, followed by afunctional statement, are intended to define and cover whateverstructural, physical, chemical or electrical element or structure maynow or in the future exist for carrying out the recited function,whether or not precisely equivalent to the embodiment or embodimentsdisclosed in the specification above; and it is intended that suchexpressions be given their broadest interpretation.

The inventors have continued to make improvements to their inventionregarding use of low pressure, heated catheter, etc.

Prior Art Patents

Lee in U.S. Pat. No. 3,298,371 teaches a freezing probe to be used inneurosurgery. Attached to this freezing probe is a heater. This heateris provided in the event the insulation on the exterior of the probe isinadequate to thermally isolate non-target tissue surrounding the probe.In this way, non-target areas will not be affected by the cold, and onlythe cold probe tip will be presented to the target area.

Thomas U.S. Pat. No. 3,507,283 shows a cryosurgical probe which employsheating wires along the external surface of the instrument. Also shownby Thomas is a cover of heat shrinkable polytetrafluoroethylene toprotect the user's hand from the cold.

Chang in U.S. Pat. No. 5,400,602 teaches various types of plasticmaterials used for cryotubing which remain flexible during use.

Griswold U.S. Pat. No. 5,658,276 teaches a cryoprobe with a heatedexterior so that areas of the body not being treated by the probe arenot damaged by the cold instrument. The heat is produced by abattery-energized resistive wire wrapped around the external surface ofthe probe.

U.S. Pat. No. 5,800,488 to Crockett teaches a cryoprobe whereindifferent methods are used to heat the external surface.

The inventors have continued to make improvements to their invention.They have produced a heated catheter. The heated catheter in a preferredembodiment is a composite constructed of three different materials; inthree different layers. The catheter itself (as the first layer) is madeof extruded polyimide. Surrounding the first layer (the catheter) is alayer of magnetic wire wrapped around the outer diameter of thepolyimide catheter. As a top or final layer, there is supplied a thinpolyester heat shrink.

More specifically, the heated catheter (cryocatheter) can be defined asan extruded polyimide tube (O.D. 0.092″). Over the catheter is wrapped alayer of magnetic copper wire (0.007″ diameter). A number of differentdiameter wires are available. The inventors put together prototypes with0.003″ diameter wire, 0.002″ diameter wire, 0.005″ diameter wire, etc. A0.007″ diameter wire was the best for the desired voltage, but theinvention does not exclude the use of wires of other diameters.

The wrappings of wire that functioned the best were 8 wraps per inch (asingle strand was run the length of the catheter, and the wrapping wasapplied back over this single strand to complete the electrical loop.Double strand wrapping with the wrap spacing (up to 25 wraps per inch)would be operative.

A selected preferred voltage for application is 12 volts and 1 amp.Voltages of 5, 12, 17 and 24 volts have been tested. The important thingto keep in mind is that different diameter wires work well if wrapped tothe correct density and heated with the appropriate amount of voltages.

The final layer employed is a thin (0.00025″) polyester heat shrink.This heat shrink serves to hold the wire in place and to seal the wirefrom patient contact.

The hub, or connection of the catheter to the cryo-system, has beendesigned to incorporate the electrical contacts required by the heatingsystem.

Advantages of the Heated Catheter

The heated catheter provides a number of advantages over a traditionalcatheter:

Polyimide, the Cryo-catheter material base, acts as a strong insulatorand transports the liquid nitrogen with minimal thermal temperature lossresulting in a shorter time to achieve the clinically required cryoburn.

The heating mechanism allows the catheter to be removed from theendoscope lumen immediately following the cryo-therapy. Using atraditional catheter, the catheter is frozen into the endoscope lumenfor 30-40 seconds following the therapy. This freezing to the endoscopelumen may result in damage to the endoscope.

In an embodiment of the invention, the bleeder valve has been found tobe unnecessary so long as low pressure can be maintained by other means.In the improved embodiment, a cryoburn is carried out without the needfor a bleeder valve. In this new embodiment with the tank pressure at 45psi and the catheter being a 9 french, the cryo-procedure took 4 minutesand 50 seconds. With a 10 french catheter using 45 psi, thecryo-procedure took 2 minutes and 50 seconds to achieve a cryoburntemperature. With the bleeder valve, it takes 10-20 seconds to achievecryoburn. The ideal low pressures operative for this invention should bein the range of 3-45 psi. The most ideal pressure is determinable bythose skilled in the art.

It is clear from experiments performed that a bleeder valve is notabsolutely essential to this invention since low pressure cryoablationcan be carried out through low head pressure in the storage tank orthrough selection of the proper inner diameter of the catheter. Based onexperiments carried out with the bleeder valve embodiment a shorter timeperiod is required for cryoburn.

Insulated Fittings

The new fittings on the device will be vacuum insulated. This will keepthe fittings from frosting or feeling super cool to the human touch.

In addition, the hub or connective fittings which couple the catheter tothe cryosystem have been redesigned and improved to accommodateelectrical contacts required for the heating system.

The inventors have continued to make improvements to their cryogenicheated catheter. Among the improvements contemplated by the inventors isthe heating coil on the heated catheter being energized in “series” orthat the catheter is heated with a continuous length energized from twoends. Also contemplated is a catheter with the heating element inparallel. This will result in heating short segments (5-10 segments percatheter) quickly and with more energy.

The inventors may adjust the wrappings of the heating coil so that theloops touch one another. A parallel electrical transfer may benecessary.

It may be feasible to employ flat wire (square wire) as opposed to roundwire. Whether to use series or parallel spacing will be determined basedon individual use.

The inventors contemplate coating the gap between the wires with a heatsink which will act to absorb radiated heat from the heating coil todispense the heat to the outside of the catheter.

Also contemplated by the inventors is a spray coat or liquid paint of anichrome conductor. In this embodiment the entire catheter could beenergized quite quickly.

The inventors envision alternate means for diverting freezingtemperatures from non-target areas. Examples of such diverting means isa polystyrene tape to function as an insulator. Alternatively, thecatheter may be made of polystyrene or some other insulating material.

During the cryoburn the heat of the catheter remains active. Thisprevents the accidental injury to non-target tissue.

Obviously, many modifications may be made without departing from thebasic spirit of the present invention. Accordingly, it will beappreciated by those skilled in the art that within the scope of theappended claims, the invention may be practiced other than has beenspecifically described herein.

What is claimed is:
 1. A method of treating internal lesions of theintestinal tract comprising applying to such lesions a low pressurecryogenic spray to ablate said lesions wherein the low pressure isdefined as being in the range of 3-45 psi, and wherein the cryogenicspray is applied by means of a heated catheter so that non-target areasare not affected by the cold ofthe catheter.